Chiral diol sulfones are advanced intermediates used in preparing statins, a class of compounds useful as HMG CoA reductase inhibitors. In particular, chiral diol sulfones are employed in preparing statins in which an unsaturated carbon-carbon bond (R1—CH═CH—R2) is to be formed such as is the case in the antilipemic drugs cerivastatin, fluvastatin, pitavastatin and rosuvastatin.
A method for preparing chiral diol sulfones is described in WO 2002/098854 and WO 2001/096311. In these citations, a sulfone is prepared from an alcohol, more in particular tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl) acetate known as “Kaneka alcohol”. The preparation of such an alcohol is described in EP 1024139.
Formation of unsaturated carbon-carbon bonds can be realized by the so-called Julia-Kocienski olefination (for a review see Aïssa (Eur. J. Org. Chem. 2009, 1831-1844)) between an aldehyde and the sulfones mentioned above in the presence of a base. Well-advocated bases in this respect are lithium hexamethyldisilazane (LiHMDS), potassium hexamethyldisilazane (KHMDS) and sodium hexamethyldisilazane (NaHMDS) as these bases are known for their versatility in controlling the E/Z-ratio of the products. A major drawback of these bases is that they can easily form unwanted side products which results in lower yields and difficult recovery and purification procedures.
It is an object of the present invention to provide a process wherein improved yields are obtained in comparison to the Julia-Kocienski olefination in the presence of KHMDS, LiHMDS or NaHMDS.